| abstract |
Interferon gamma analog (IFNγ), where the fraction that mediates binding to its natural receptor is at least functionally interrupted and where the analog comprises a signaling fraction capable of mediating intracellular IFNγ activity, where the signaling fraction comprises in the C-terminal end of the analogue a sequence selected from the group consisting of: (a) the amino acid sequence KFEVNNPQVQRQAFNELIRVVHQLLPESSLRKRKRSR; (b) the amino acid sequence YSVTDLNVQRKAIHELIQVMAELSPAAKTGKRKRSQ; (c) an amino acid sequence that shows at least 90% identity with (a) or (b) as long as the intracellular signaling activity is maintained; (d) the amino acid sequence (a) or (b) where at most amino acid residues are eliminated, added or substituted, provided that signaling activity, for example nuclear translocation, is maintained; (e) the consensus sequence Vxxxx [V / I] Q [R / H] [Q / K] A [F / V / I] [N / H] ELI [R / Q] Vx [H / A] [ Q / E] L [L / S] P [E / A] [S / A] [S / A] [L / K] xxKRKRS where x is any amino acid residue; and (f) the sequence Xaa1Xaa2Xaa3Xaa4 Val Xaa5 Xaa6 Xaa7 Xaa8 Xaa9 Gln Xaa10 Xaa11 Ala Xaa12 Xaa13 Glu Leu Ile Xaa14 Val Xaa15 Xaa16 Xaa17 Leu Xaa18 Pro Xaa19 Xaa20 Xaa21 Xaa22 Xaa23Lys Arg Lys Arg Ser Xaa24 Xaa25 where Xaa1, Xaa2, Xaa3 Xaa4 Xaa6 Xaa11, Xaa13, Xaa14, Xaa16 Xaa17, Xaa18 Xaa19 Xaa20 Xaa21 Xaa22 Xaa23 Xaa24 and Xaa25 is any amino acid residue Xaa5 is Asn or Thr Xaa7 is Pro or Leu Xaa8 is Gln or Asn Xaa9 Val, Ile or Leu Xaa10 is Arg, His or Lys Xaa12 is Phe, Val or Ile Xaa15 is Val, Ile or Met said signaling fraction is provided in its N-term, optionally via a linker, with at least one selection domain capable of binding to a cell surface receptor other than IFNγ receptor, where said selection domain can bind to the PDGFβ receptor, the mannose-6 phosphate / insulin-like growth factor-II receptor (M6P / IGF2R), the asialoglycoprotein receptor (ASGP) or the mannose receptor ( CD 206). |